SCREENING PLATELETS INTERACTIONS WITH SURFACE GRADIENTS Most biomaterials become coated with a protein layer within seconds after being exposed to a protein-containing environment such as blood. It is generally accepted that the protein layer build-up at the biomaterial - host interface is largely responsible for the host's reactions to the biomaterial. We propose designing new types of surface gradients to understand how different combinations of surface parameters mediate ad-layers of blood proteins and subsequent platelet interactions. We anticipate that the knowledge gained in the proposed research will lead us closer to truly hemocompatible biomaterials. The general aims of the proposed research are to: engineer new biomaterial interfaces with controlled surface gradients of selected molecular parameters, and use them to test for platelet adhesion and activation after they've acquired a protein layer from blood. We propose to design the following spatial gradients: - gradient of hydrophobic and hydrophilic nano-domains, - gradient of surface charges and dipoles, and - gradient of surface density of hydrophilic polymers with different chain rigidity. We will study the effects that each of the gradient parameters have on: (i) affinity towards adsorbing proteins from blood plasma or serum, (ii) distribution, dynamics and mobility of adsorbed blood proteins, and (iii) adhesion and activation of platelets. The use of spatially controlled molecular gradients will enable us to rapidly pre-screen the effect(s) that a given magnitude and the combination of surface properties has on blood protein binding and platelet adhesion and activation. The pre-screening phase will be followed by a transposition of a particular local gradient region at which we found minimal platelet adhesion into a uniform, non-gradient version of the same surface molecular structure which will be re- tested for the same effect. The novelty in our approach is in the parallelism that is built-in in the molecular gradient approach. By using gradients of several key surface parameters and correlating their local chemistry and microstructure with the extent of local platelet adhesion and activation after blood protein deposition (all measured under otherwise identical experimental conditions) we expect to obtain information about which critical parameters are required for engineering biomaterial interfaces that resist platelet adhesion and activation.